Allergan announced the FDA approved a New Drug Application for Vraylar for the treatment of depressive episodes associated with bipolar depression.
Willie Earley, MD
Allergan and Gedeon Richter announced that the US Food and Drug Administration has approved a New Drug Application for cariprazine (Vraylar®) for the treatment of depressive episodes in adults with bipolar depression (BPD).
With the FDA approval, the oral, once-daily becomes the first dopamine and serotonin partial agonist to treat the full spectrum of bipolar I symptoms in manic, mixed, and depressive episodes. The treatment received approval based on the results 3 pivotal trials — a post hoc analysis of the 3 trials was presented at the 2019 Annual Meeting of the American Psychiatric Association.
“What this analysis really does is really highlight the fact that cariprazine works in the middle as well when patients begin to have some symptoms of either of the opposite pole,” said Willie Earley, MD, associate vice president of clinical development at Allergan.
In the analysis, investigators pooled data from 3 studies (NCT01396447, NCT02670538, NCT02670551) that demonstrated the efficacy of cariprazine in 1.5mg and 3mg per day doses compared to placebo for patients with BPD. A total of 1383 were identified in the 3 studies and 808 (58.4%) had BPD and concurrent manic symptoms.
Efficacy outcomes of the 3 studies included least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale(MADRS) total score, Hamilton Depression Rating Scale total score (HAMD), and Clinical Global Impressions-Severity (CGI-S) score.
Investigators found that LS mean difference for MADRS score change compared with placebo was in favor of cariprazine 1.5mg (-2.5, P=.0033) and 3mg (-2.9, P=.0010) in patients with manic symptoms and for cariprazine 1.5mg (-3.3, P=.0008) in patients without manic symptoms. Additionally, LS mean difference compared to placebo for HAMD total score change was in favor of cariprazine 1.5mg and 3mg (-1.9 and -1.5; P<.05 both) in patients with manic symptoms and for cariprazine 1.5mg in patients without manic symptoms. In CGI-S score change, the LS mean difference compared to placebo was greater for cariprazine 1.5mg (-0.24; P<.05) and 3mg (-0.25; P<.05) in patients with manic symptoms and in patients without manic symptoms (-0.40 and -0.26; P<.05 both).
Investigators noted that rates of MADRS response and remission, respectively, were significantly greater for cariprazine 1.5mg (46.6% and 31.3%; P<.05 both) and 3mg (49.8% and 31.4%; P<.01 both) compared to placebo (37.8% and 21.0%) in patients with manic symptoms and for cariprazine 1.5mg (45.2% and 32.3%; P<.05 both) compared to placebo (33.3% and 20.7%) in patients without manic symptoms. Rates of CGI-S remission were significantly greater than placebo for all cariprazine doses in both patient subgroups.
Investigators found that changes in metabolic parameters were generally similar between the cariprazine and placebo groups in both BPD and bipolar mania studies. The common adverse events reported in the trials analyzed were nausea, akathisia, restlessness, and extrapyramidal symptoms.
“Treating bipolar disorder can be very difficult because people living with the illness experience a range of depressive and manic symptoms, sometimes both at the same time, and this FDA approval gives healthcare providers a new option to treat the full spectrum of bipolar I disorder symptoms, specifically manic, mixed, and depressive episodes, with just one medication,” said Stephen Stahl, PhD, lead author of the analysis and professor of psychiatry at the University of California San Diego.
This study, titled “Cariprazine Efficacy in Patients with Bipolar Depression and Concurrent Manic Symptoms,” was presented at APA 2019.